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dc.contributor.advisor Hartgerink, Jeffrey D
dc.contributor.advisor Matsuda, Seiichi P
dc.creatorAcevedo-Jake, Amanda M
dc.date.accessioned 2017-08-01T17:56:11Z
dc.date.available 2018-05-01T05:01:07Z
dc.date.created 2017-05
dc.date.issued 2017-04-25
dc.date.submitted May 2017
dc.identifier.citation Acevedo-Jake, Amanda M. "Design, Structure and Applications of Collagen-Mimetic Peptides." (2017) Diss., Rice University. http://hdl.handle.net/1911/96078.
dc.identifier.urihttp://hdl.handle.net/1911/96078
dc.description.abstract The collagen triple helix is a unique protein fold found in all domains of life where is has diverse roles from imparting structure and strength to tissue, to initiating an immune response. While many factors affecting the structure and stability of the triple helix have previously been elucidated, much remains unknown about collagen. Using collagen-mimetic peptides, it is possible to investigate the molecular structure of the triple helix, determine new pairwise interactions of amino acids, characterize disease models and also create designer collagens that will preferentially hybridize to natural collagen-rich tissue. First a selective labeling scheme is used to thoroughly characterize a well-folded triple helical region, and then to determine the degree of localized unfolding at the N- and C-termini. Though terminal fraying extends farther than previously shown, small sequence alterations at the N-terminus have a drastic influence on local stability (~15C). Next, a single register heterotrimeric mimic of the type I collagen disease Osteogenesis Imperfecta is used to investigate single point glycine mutations in the B chain, the A chain or both chains. Unlike past reports, a combination of NMR analysis and molecular modelling is used to generate structures of the mutated helices and visualize the underlying mechanisms of helix destabilization in OI. For the first time it is proven that these mutations cause compositional as well as structural disruptions. Additionally, while several hundred pairwise interactions are possible in the triple helix, to date only two interactions are wellunderstood and commonly incorporated into CMP design. To expand on the library of known interactions, the structure and stability of helices containing serine, threonine, phospho-serine and phospho-threonine were investigated. Notably, when phospho-serine is paired with lysine a new highly stabilizing (49.5 C) axial interaction is possible. Finally, the design of a collagen type II targeting peptide is described, and NMR, CD and confocal microscopy are used to investigate the hybridization of the synthetic peptide with the natural partner strands.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.subjectcollagen
protein design
dc.title Design, Structure and Applications of Collagen-Mimetic Peptides
dc.date.updated 2017-08-01T17:56:11Z
dc.type.genre Thesis
dc.type.material Text
thesis.degree.department Chemistry
thesis.degree.discipline Natural Sciences
thesis.degree.grantor Rice University
thesis.degree.level Doctoral
thesis.degree.name Doctor of Philosophy
dc.embargo.terms 2018-05-01


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